MicroRNA biomarkers for early detection of prostate cancer

DESCRIPTION (provided by applicant): Prostate cancer (PrCa) is the most commonly diagnosed cancer in American men, with over 218,000 new cases diagnosed each year. It is second only to lung cancer in cancer mortality among men, and approximately 1 man in 5 will be diagnosed during his lifetime. When it is detected early, PrCa can be cured. In contrast, patients with metastatic prostate cancer have very low survival rates. The early and accurate diagnosis of PrCa patients is critical for the successful manag ement of the disease. While prostate specific antigen testing (PSA) and digital rectal exam have improved the care of PrCa patients, the false positive and false negative rates of the PSA test limit its applicability for many patients. Diagnostic assays th at can overcome the shortcomings of the PSA tests would be welcomed by both caregivers and patients. In this project we will explore the development of a microRNA (miRNA)-based diagnostic test for PrCa that can be used in combination with PSA to provide mo re accurate cancer screening. We have developed methods to isolate and detect miRNAs in biofluids. Our preliminary data indicated that these are stable, easy to detect and differentially expressed in the circulating biofluids of PrCa patients. In Aim 1 of this proposal we will test a panel of miRNA biomarkers, identified from our initial studies, for their ability to differentiate PrCa patients, patients with benign prostatic hyperplasia and normal aged matched controls. In Aim 2 we will use Asuragen's Disc ovArray miRNA microarray system to expand our miRNA discovery to find biomarker candidates that can be used with PSA to distinguish hard to resolve clinical samples. We anticipate that the completed studies will lead to the development of simple molecular diagnostic assay that can be used in the clinic. Phase II of this grant would address more rigorous validation of the biomarker set using samples collected at clinical laboratories. Additionally, we will explore further the idea that a miRNA-based assay ma y have high predictive value in the absence of PSA information. Following successful validation, we will explore optimization of qRT-PCR parameters and relevant controls for assembling an assay for clinical testing. PUBLIC HEALTH RELEVANCE:Prostate cancer continues to be the second leading cause of cancer deaths in males despite the availability of simple clinical screening tests. Our work may lead to the development of cutting-edge microRNA-based molecular diagnostic tests that can be combined with current clinical tests to provide more accurate detection of early prostate cancer and reduce the number of deaths due to prostate cancer.